Targeting AMP-Activated Protein Kinase in Aging-Related Cardiovascular Diseases

Tian, Li; Ma, Nan; Yin, Yulong; Yu, Lu; Ma, Heng

doi:10.14336/ad.2019.0901

Cited by 38 publications

(25 citation statements)

References 92 publications

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“…For many years, it has been well-known that regular physical exercise can attenuate the major hallmarks of aging and promote health span by slowing down age-related degenerative processes [ 60 , 61 , 62 ]. Indeed, as we age, the loss of muscle mass and the risks of heart disease and dementia increases, and immune function becomes increasingly impaired [ 63 ]. For example, human aging is associated with skeletal muscle atrophy and functional impairment (sarcopenia), which can be partially reversed following six months of resistance exercise training [ 64 ].…”

Section: Ampk Signalingmentioning

confidence: 99%

Key Signaling Pathways in Aging and Potential Interventions for Healthy Aging

Zhang

Wang

et al. 2021

Cells

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Aging is a fundamental biological process accompanied by a general decline in tissue function. Indeed, as the lifespan increases, age-related dysfunction, such as cognitive impairment or dementia, will become a growing public health issue. Aging is also a great risk factor for many age-related diseases. Nowadays, people want not only to live longer but also healthier. Therefore, there is a critical need in understanding the underlying cellular and molecular mechanisms regulating aging that will allow us to modify the aging process for healthy aging and alleviate age-related disease. Here, we reviewed the recent breakthroughs in the mechanistic understanding of biological aging, focusing on the adenosine monophosphate-activated kinase (AMPK), Sirtuin 1 (SIRT1) and mammalian target of rapamycin (mTOR) pathways, which are currently considered critical for aging. We also discussed how these proteins and pathways may potentially interact with each other to regulate aging. We further described how the knowledge of these pathways may lead to new interventions for antiaging and against age-related disease.

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Section: Ampk Signalingmentioning

confidence: 99%

Key Signaling Pathways in Aging and Potential Interventions for Healthy Aging

Zhang

Wang

et al. 2021

Cells

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“…These further result in endothelial dysfunction due to (1) nitric oxide inhibition in the endothelial cells of the blood vessels and (2) increased inflammation and fibrosis[ 109 ], eventually leading to increased risk of atherosclerotic CVD (marked as subsection A in Figure 1 ). Interestingly, many studies found that AMPK has a protective role in cardiac injury by acting against oxidative stress and turns into a potential therapeutic target in patients with diabetes and COVID-19[ 110 , 114 ]. Besides this link between oxidative stress, DM, and CVD, some recent studies have also pointed out a possible role of oxidative stress in the pathogenesis of COVID-19 related infections[ 112 , 113 , 115 , 116 ]; however, this is beyond the scope of this review.…”

Section: How Can the Interplay Between Dm And Covid-19 Increase The Rmentioning

confidence: 99%

Bidirectional link between diabetes mellitus and coronavirus disease 2019 leading to cardiovascular disease: A narrative review

Viswanathan¹,

Puvvula²,

Jamthikar³

et al. 2021

WJD

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Coronavirus disease 2019 (COVID-19) is a global pandemic where several comorbidities have been shown to have a significant effect on mortality. Patients with diabetes mellitus (DM) have a higher mortality rate than non-DM patients if they get COVID-19. Recent studies have indicated that patients with a history of diabetes can increase the risk of severe acute respiratory syndrome coronavirus 2 infection. Additionally, patients without any history of diabetes can acquire new-onset DM when infected with COVID-19. Thus, there is a need to explore the bidirectional link between these two conditions, confirming the vicious loop between “DM/COVID-19”. This narrative review presents (1) the bidirectional association between the DM and COVID-19, (2) the manifestations of the DM/COVID-19 loop leading to cardiovascular disease, (3) an understanding of primary and secondary factors that influence mortality due to the DM/COVID-19 loop, (4) the role of vitamin-D in DM patients during COVID-19, and finally, (5) the monitoring tools for tracking atherosclerosis burden in DM patients during COVID-19 and “COVID-triggered DM” patients. We conclude that the bidirectional nature of DM/COVID-19 causes acceleration towards cardiovascular events. Due to this alarming condition, early monitoring of atherosclerotic burden is required in “Diabetes patients during COVID-19” or “new-onset Diabetes triggered by COVID-19 in Non-Diabetes patients”.

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“… 29 Recent evidences have shown that AMPK protects against oxidative stress in the heart under various pathological conditions. 30 Specifically, AMPK has been reported to exert antioxidant effects in the cardiovascular system by inhibiting the expression and activity of NOX. 31 , 32 Here, we found that SMS markedly increased AMPKα phosphorylation at Thr172 in the myocardium exposed to long-term high glucose.…”

Section: Discussionmentioning

confidence: 99%

ShengMai-San Attenuates Cardiac Remodeling in Diabetic Rats by Inhibiting NOX-Mediated Oxidative Stress

Lu¹,

Zhu²,

Wang³

et al. 2021

DMSO

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Background and Purpose ShengMai-San (SMS) is traditionally used to treat ischemic cardiovascular and cerebrovascular diseases. Recently, several studies have reported the cardioprotective effects of SMS in diabetic animals. However, the potential mechanisms have not yet been fully elucidated. In this study, we investigated whether SMS exerts a beneficial effect in diabetic cardiomyopathy (DCM) by alleviating NADPH oxidase (NOX)-mediated oxidative stress. Methods SD rats were randomly divided into a negative control group (NC), diabetes mellitus group (DM) and SMS-treated group (SMS). The myocardial structure alterations, apoptosis and biomarkers of oxidative stress were observed. Moreover, to explore the protective mechanism of SMS, the activation of AMPKα, expression and translocation of NOX-related proteins were assessed. Results Diabetes led to excessive collagen content, fibrosis, and apoptosis in the myocardium. Oxidative stress in diabetic hearts was indicated by low levels of T-AOC, high levels of 8-iso-PGF2α and 8-OHdG, inactivation of AMPKα, elevated expression of NOX2 and NOX4 and translocation of NOX isoforms p47phox and p67phox. Treatment with SMS for 10 weeks resulted in the alleviation of diabetes-associated myocardial structure abnormalities and apoptosis. Additionally, SMS attenuated the accumulation of oxidative stress markers in myocardial tissue. Further investigation showed that SMS was able to reverse the levels of oxidative stress-associated proteins NOX2 and NOX4 in the DM rats. Moreover, SMS treatment blunted the translocation of NADPH oxidase isoforms p47phox and p67phox as well. Furthermore, SMS promoted the activation of AMPK in the cardiac tissue of diabetic rats. Conclusion These findings indicate that SMS exhibits therapeutic properties against diabetic cardiomyopathy by attenuating myocardial oxidative damage via activation of AMPKα and inhibition of NOX signaling.

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Targeting AMP-Activated Protein Kinase in Aging-Related Cardiovascular Diseases

Cited by 38 publications

References 92 publications

Key Signaling Pathways in Aging and Potential Interventions for Healthy Aging

Key Signaling Pathways in Aging and Potential Interventions for Healthy Aging

Bidirectional link between diabetes mellitus and coronavirus disease 2019 leading to cardiovascular disease: A narrative review

ShengMai-San Attenuates Cardiac Remodeling in Diabetic Rats by Inhibiting NOX-Mediated Oxidative Stress

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